hung-jung Wang

hung-jung Wang
Taipei Medical University Hospital | TMUH · Department of Radiology

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39
Publications
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Introduction
Skills and Expertise

Publications

Publications (39)
Article
Full-text available
Rationale: One of the most common metabolic defects in cancers is the deficiency in arginine synthesis, which has been exploited therapeutically. Yet, challenges remain, and the mechanisms of arginine-starvation induced killing are largely unclear. Here, we sought to demonstrate the underlying mechanisms by which arginine starvation-induced cell de...
Article
Full-text available
Arginine plays diverse roles in cellular physiology. As a semi-essential amino acid, arginine deprivation has been used to target cancers with arginine synthesis deficiency. Arginine-deprived cancer cells exhibit mitochondrial dysfunction, transcriptional reprogramming and eventual cell death. In this study, we show in prostate cancer cells that ar...
Article
Full-text available
PKM2 is a key metabolic enzyme central to glucose metabolism and energy expenditure. Multiple stimuli regulate PKM2’s activity through allosteric modulation and post-translational modifications. Furthermore, PKM2 can partner with KDM8, an oncogenic demethylase and enter the nucleus to serve as a HIF1α co-activator. Yet, the mechanistic basis of the...
Article
Full-text available
During the evolution into castration or therapy resistance, prostate cancer cells reprogram the androgen responses to cope with the diminishing level of androgens, and undergo metabolic adaption to the nutritionally deprived and hypoxia conditions. AR (androgen receptor) and PKM2 (pyruvate kinase M2) have key roles in these processes. We report in...
Article
Full-text available
Defective arginine synthesis, due to the silencing of argininosuccinate synthase 1 (ASS1), is a common metabolic vulnerability in cancer, known as arginine auxotrophy. Understanding how arginine depletion kills arginine-auxotrophic cancer cells will facilitate the development of anti-cancer therapeutic strategies. Here we show that depletion of ext...
Article
Cholesterol‐α‐glucosyltransferase (CGT) encoded by the type 1 capsular polysaccharide biosynthesis protein J (capJ) gene of Helicobacter pylori converts cellular cholesterol into cholesteryl glucosides. H. pylori infection induces autophagy that may increase bacterial survival in epithelial cells. However, the role of H. pylori CGT exploits lipid r...
Article
Arginine deprivation has recently emerged as a promising cancer therapy, targeting tumor metabolism. This is due to the selective silencing of argininosuccinate synthetase 1 (ASS1) gene in many cancer types, rendering them “addicted” to external arginine. PEGylated arginine deiminase (ADI-PEG20), which effectively metabolizes arginine into citrulli...
Article
Full-text available
Background/Purpose Helicobacter pylori colonizes the human stomach and contributes to chronic inflammation of the gastric mucosa. H. pylori persistence occurs because of insufficient eradication by phagocytic cells. A key factor of H. pylori, cholesterol-α-glucosyltransferase encoded by capJ that extracts host cholesterol and converts it to cholest...
Article
JMJD5, a JmjC-domain containing dioxygenase, is important for embryonic development and cancer growth. Here, we show that JMJD5 is up-regulated by hypoxia and is crucial for hypoxia-induced cell proliferation. JMJD5 interacts directly with PKM2, pyruvate kinase M2, to modulate metabolic flux in cancer cells. The JMJD5-PKM2 interaction resides at th...
Article
Lipid rafts are mainly composed of phospholipids, sphingolipids, and cholesterol and dispersed in the cell membrane; these dynamic structures amplify signaling cues into the cells. A number of pathogens and virulence factors are found to favorably interact with lipid rafts as a major route to enter cells, followed by pathogenic effects. Helicobacte...
Article
Full-text available
Shikimate kinase (SK), which catalyzes the specific phosphorylation of the 3-hydroxyl group of shikimic acid in the presence of ATP, is the enzyme in the fifth step of the shikimate pathway for biosynthesis of aromatic amino acids. This pathway is present in bacteria, fungi, and plants but absent in mammals and therefore represents an attractive ta...
Data
Chemical structure of NSC162535. (TIF)
Data
Conformational movement in the SB domain of HpSK·R57A structure. A stereo view of the superimposed binding pocket between open HpSK (blue) and R57A (magenta) structures is shown. The oxygen, nitrogen and phosphorus atoms are colored red, blue and orange, respectively. The dashed line indicates hydrogen bonds. (TIF)
Article
Full-text available
Members of protein families often share conserved structural subsites for interaction with chemically similar moieties despite low sequence identity. We propose a core site-moiety map of multiple proteins (called CoreSiMMap) to discover inhibitors and mechanisms by profiling subsite-moiety interactions of immense screening compounds. The consensus...
Data
(A) Circular dichroism profiles of HpSK in the presence or absence of various ligands. (B) Superimposition of apo and closed HpSK structures. Apo and closed structures are shown in red and green, respectively. Shikimate and phosphate are represented as sticks. The carbon, oxygen and phosphorus atoms are colored green, red, and orange, respectively....
Data
Comparison of three dose-response curves of shikimate dehydrogenase (SDH), shikimate kinase (SK), and dual enzyme (SDH and SK) activities on three compounds, NSC45611, NSC45174, and NSC162535 (specific for SK). For NSC45611 and NSC45174, at inhibitor concentrations greater than the IC90 value, the dual enzyme curves swiftly approached approximately...
Data
Atom types used for atom pair descriptors. (DOC)
Data
Superposition of nine shikimate kinases. The apo- and closed-HpSK (PDB codes: 1ZUH and 3MUF) are shown in blue and cyan, respectively. Apo form of MtSK (PDB code: 2IYT) is shown in orange, and closed-form (PDB code: 2IYQ) in yellow. The EcSK (PDB code: 1SHK) is red, and the EcSK complexed with ADP (PDB code: 2SHK) is pink. Green, brown and gray are...
Data
Conserved residues of SKs and structure-based alignment of HpSK and MtSK. Six shikimate kinases (E. coli, E. chrysanthemi, C. jejuni, A. aeolicus, M. tuberculosis and H. pylori) are aligned and shown with WebLogo program (http://weblogo.berkeley.edu/). HpSK and MtSK alignment are shown with ESPript program (http://espript.ibcp.fr/ESPript/ESPript/)....
Data
Summary of 37 pairs of orthologous targets. (DOC)
Data
Parameters used in the CoreSiMMap. (DOC)
Article
To determine the number of regulatory T cells (Tregs) in gastric mucosa of patients with gastritis, peptic ulcers and gastric cancer. This study was a retrospective analysis of gastric antrum biopsy specimens from healthy controls (n = 22) and patients with gastritis (n = 30), peptic ulcer (n = 83), or gastric cancer (n = 32). Expression of CD4, CD...
Article
Helicobacter pylori infection is an aetiological cause of gastric disorders worldwide. H. pylori has been shown to assimilate and convert host cholesterol into cholesteryl glucosides (CGs) by cholesterol-α-glucosyltransferase encoded by capJ. Here, we show that CapJ-deficient (ΔcapJ) H. pylori resulted in greatly reduced type IV secretion system (T...
Article
Upon infection of the gastric epithelial cells, the Helicobacter pylori cytotoxin-associated gene A (CagA) virulence protein is injected into the epithelial cells via the type IV secretion system (TFSS), which is dependent on cholesterol. Translocated CagA is targeted by the membrane-recruited c-Src family kinases in which a tyrosine residue in the...
Article
Helicobacter pylori (H. pylori) infection induces cytokine production and is associated with gastrointestinal diseases. This study examined the relationship of gene polymorphisms, including interleukin (IL)-1beta, -10, -8, and tumor necrosis factor-alpha (TNF-alpha), H. pylori infection, and susceptibility to gastrointestinal disorders in Taiwanese...
Article
Laminaripentaose-producing β-1,3-glucanase (LPHase), a member of glycoside hydrolase family 64, cleaves a long-chain polysaccharide β-1,3-glucan into specific pentasaccharide oligomers. The crystal structure of LPHase from Streptomyces matensis DIC-108 was solved to 1.62 Å resolution using multiple-wavelength anomalous dispersion methods. The LPHas...
Article
Full-text available
Laminaripentaose-producing beta-1,3-glucanase (LPHase), a member of glycoside hydrolase family 64, cleaves a long-chain polysaccharide beta-1,3-glucan into specific pentasaccharide oligomers. The crystal structure of LPHase from Streptomyces matensis DIC-108 was solved to 1.62 A resolution using multiple-wavelength anomalous dispersion methods. The...
Article
During 1998-2004, a total of 218 Helicobacter pylori isolates were obtained from patients who were randomised to receive one of the following regimens in a medical centre in Taiwan: lansoprazole, amoxicillin and clarithromycin (LAC) therapy; or lansoprazole, metronidazole and clarithromycin (LMC) therapy. In the LMC group, resistance rates for metr...
Article
Dehydroquinate synthase (DHQS) is a nicotinamide adenine dinucleotide (NAD)-dependent enzyme that converts 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) into 3-dehydroquinate (DHQ). Since it catalyzes the second key step in the shikimate pathway, which is crucial for the aromatic amino acid metabolism in bacteria, fungi, and plants, but not in...
Article
Full-text available
Infection with Helicobacter pylori cagA-positive strains is associated with gastritis, ulcerations, and gastric cancer. CagA is translocated into infected epithelial cells by a type IV secretion system and can be tyrosine phosphorylated, inducing signal transduction and motogenic responses in epithelial cells. Cellular cholesterol, a vital componen...
Article
Consecutive study. To investigate the changes of disc signal in intradiscal vacuum phenomenon during prolonged supine MR imaging. Increased T2 signal on MR imaging in intravertebral vacuum cleft during prolonged supine positioning has been described, but no sequential observation of the intervertebral discal signal change in intervertebral disc vac...
Article
To validate carotid duplex sonography (CDS) in diagnosis of intracranial dural arteriovenous fistulas (AVFs) against the standard of cerebral catheter angiography. We investigated 35 patients with dural AVFs and 64 patients without dural AVFs confirmed by the catheter angiographic studies. Twenty CDS parameters in 4 categories, including resistive...

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